PhD. Positions


 

How to apply:

Please note that all applications absolutely need to be placed through the HBGIS website:  www.hbigs.uni-heidelberg.de !!

Salary:  

Fully-funded doctoral position as per German regulations (TVL-13, 65%)

Contract length:

PhD positions typically run for 3 years with the option of extending by 1 year.

 



 

Neural circuits mediating analgesia


Job ID: SFB1158PhD_RK

Project leader: Rohini Kuner

Email:

Application Deadline:

30 September 2019

Start of the project:

01 January 2020

Project Description: 

Chronic pain is a major health problem word-wide. Our laboratory works on elucidating mechanisms and circuits underlying chronic pain (see, for example, Tan et al. Nature Communications 2019; Tan et al. Nature Neuroscience 2017; Vicuna et al. Nature Medicine 2015; Kuner and Flor, Nature Reviews Neuroscience 2016). We are seeking PhD students in projects aimed at elucidating brain pathways and mechanisms involved in chronic pain in mouse models. Methods include viral-based circuit mapping, labelling cellular engrams, optogenetics, chemogenetics, in vivo multiphoton imaging, in vivo electrophysiology, neuromodulation and behavior.

The prefrontal cortex is implicated in chronic pain, as well as other emotional states, such as fear and anxiety. This project will address the hypothesis is that neural circuits underlying pain and those involved in other prefrontal functions, such as fear or stress response, are distinct under naive conditions, but may show strong interactions over chronic pain states. It will make use of highly modern molecular engramming tools, such as binary, tetracycline-inducible, c-Fos promoter-based activity mapping system, to label ensembles neurons selectively activated in specific pain or fear states. Employing optogenetic approaches, we will then manipulate cellular engrams in behavioral assays of chronic pain in mice.

References:

  1. Tan LL, Oswald MJ, Heinl C, Retana Romero OA, Kaushalya SK, Monyer H, Kuner R.Gamma oscillations in somatosensory cortex recruit prefrontal and descending serotonergic pathways in aversion and nociception. Nat Commun. 2019 Feb28;10(1):983.
  1. Tan LL, Pelzer P, Heinl C, Tang W, Gangadharan V, Flor H, Sprengel R, Kuner T, Kuner R. A pathway from midcingulate cortex to posterior insula gates nociceptive hypersensitivity. Nat Neurosci. 2017 Nov;20(11):1591-1601
  1. Kuner R, Flor H. Structural plasticity and reorganisation in chronic pain. Nat Rev Neurosci. 2016 Dec 15;18(1):20-30.
  1. Vicuña L, Strochlic DE, Latremoliere A, Bali KK, Simonetti M, Husainie D, Prokosch S, Riva P, Griffin RS, Njoo C, Gehrig S, Mall MA, Arnold B, Devor M, Woolf CJ, Liberles SD, Costigan M, Kuner R. The serine protease inhibitor SerpinA3N attenuates neuropathic pain by inhibiting T cell-derived leukocyte elastase. Nat Med. 2015 May;21(5):518-23. 

 

Methods that will be used

viral-based circuit mapping, labelling cellular engrams, optogenetics, chemogenetics, neuromodulation and behavior

Collaboration Partners:

Thomas Kuner, Heidelberg University

Johannes Gräf, Switzerland

 

Profile of candidate’s qualification

Applicants must have a strong background and training in neuroscience and preferably have experience in at least 2 of the methods described above. 

Keywords:

Pain chronicity, transgenic mice, molecular tools, optogenetics, behaviour

 

Neural circuits mediating analgesia


Job ID: SFB1158PhD_RK_2

Project leader: Rohini Kuner

Email:

Application Deadline:

30 September 2019

Start of the project:

01 January 2020

Project Description: 

Chronic pain is a major health problem word-wide. Our laboratory works on elucidating mechanisms and circuits underlying chronic pain (see, for example, Tan et al. Nature Communications 2019; Tan et al. Nature Neuroscience 2017; Vicuna et al. Nature Medicine 2015; Kuner and Flor, Nature Reviews Neuroscience 2016). We are seeking PhD students in projects aimed at elucidating brain pathways and mechanisms involved in chronic pain in mouse models. Methods include viral-based circuit mapping, labelling cellular engrams, optogenetics, chemogenetics, in vivo multiphoton imaging, in vivo electrophysiology, neuromodulation and behavior.

This project involves in vivo recordings of brain oscillatory activity in awake behaving mice and addressing their relevance to pain chronicity.  A related goal is to address circuits mediating analgesia induced by brain stimulation approaches, such as transcranial magnetic stimulation, using transgenic mice and the above-described methods. The approaches will enable deep insights into activity patterns and circuits mediating chronic pain and applying this knowledge to improve brain stimulation paradigms in pain therapy.

References:

  1. Tan LL, Oswald MJ, Heinl C, Retana Romero OA, Kaushalya SK, Monyer H, Kuner R.Gamma oscillations in somatosensory cortex recruit prefrontal and descending serotonergic pathways in aversion and nociception. Nat Commun. 2019 Feb28;10(1):983.
  1. Tan LL, Pelzer P, Heinl C, Tang W, Gangadharan V, Flor H, Sprengel R, Kuner T, Kuner R. A pathway from midcingulate cortex to posterior insula gates nociceptive hypersensitivity. Nat Neurosci. 2017 Nov;20(11):1591-1601
  1. Kuner R, Flor H. Structural plasticity and reorganisation in chronic pain. Nat Rev Neurosci. 2016 Dec 15;18(1):20-30.
  1. Vicuña L, Strochlic DE, Latremoliere A, Bali KK, Simonetti M, Husainie D, Prokosch S, Riva P, Griffin RS, Njoo C, Gehrig S, Mall MA, Arnold B, Devor M, Woolf CJ, Liberles SD, Costigan M, Kuner R. The serine protease inhibitor SerpinA3N attenuates neuropathic pain by inhibiting T cell-derived leukocyte elastase. Nat Med. 2015 May;21(5):518-23. 

 

Methods that will be used

electrophysiology, in vivo imaging, optogenetics, chemogenetics, neuromodulation and behavior

Collaboration Partners:

Catherine Belzung, France

Nicolas Renier, France

 

Profile of candidate’s qualification

Applicants must have a strong background and training in neuroscience and preferably have experience in at least 2 of the methods described above. 

Keywords:

Pain chronicity, neural circuits, transgenic mice, electrophysiology, optogenetics, behaviour

 

Neuron-Glia interaction in chronic pain: characterization of cell type-specific transmitter release and their downstream signaling


Job ID: SFB 1158_Kuner_Simonetti0119

Project leader: Rohini Kuner / Manuela Simonetti

Email:

Application Deadline:

30 September 2019

Start of the project:

01 January 2020

Project Description: 

Many form of chronic pain, that are poorly responding to common therapies, can be treated with antidepressants, but the mechanism is unknown. Furthermore, in chronic pain conditions, microglia and astrocytes become reactive and exhibit dysregulated Ca2+ signaling, which in turn might lead to increased or decreased gliotransmitter release. The central question of this project is to understand if and how glia cells are mediating the analgesic effect of antidepressants. In particular, we aim to identify molecules released specifically by astrocytes and microglia in basal and neuropathic state, characterize the signaling pathways that will be activated and their modulation in presence of antidepressant. 
We will address this question studying astrocytes and microglia structural and functional dynamics in neuropathic pain conditions in mice in brain as well as in spinal cord. We will use genetic, viral and pharmacologic tools to modulate glia signaling specifically in one cell types in vivo and test behavioral effects as read outs.

References:

  1. Paldy E, Simonetti M, Worzfeld T, Bali KK, Vicuña L, Offermanns S, Kuner R. Semaphorin 4C Plexin-B2 signaling in peripheral sensory neurons is pronociceptive in a model of inflammatory pain. Nat Commun. 2017 Aug 2;8(1):176. 

    Agarwal A, Wu PH, Hughes EG, Fukaya M, Tischfield MA, Langseth AJ, Wirtz D, Bergles DE. Transient Opening of the Mitochondrial Permeability Transition Pore Induces Microdomain Calcium Transients in Astrocyte Processes. Neuron. 2017 Feb 8;93(3):587-605.e7 

    Vicuña L, Strochlic DE, Latremoliere A, Bali KK, Simonetti M, Husainie D, Prokosch S, Riva P, Griffin RS, Njoo C, Gehrig S, Mall MA, Arnold B, Devor M, Woolf CJ, Liberles SD, Costigan M, Kuner R. The serine protease inhibitor SerpinA3N attenuates neuropathic pain by inhibiting T cell–derived leukocyte elastase. Nat. Med. 2015;21:518–523. 

    Simonetti M, Agarwal N, Stösser S, Bali KK, Karaulanov E, Kamble R, Pospisilova B, Kurejova M, Birchmeier W, Niehrs C, Heppenstall P, Kuner R. Wnt-Fzd signaling sensitizes peripheral sensory neurons via distinct noncanonical pathways. Neuron 2014;83:104–121. 

    Simonetti M, Hagenston AM, Vardeh D, Freitag HE, Mauceri D, Lu J, Satagopam VP, Schneider R, Costigan M, Bading H, Kuner R. Nuclear Calcium Signaling in Spinal Neurons Drives a Genomic Program Required for Persistent Inflammatory Pain. Neuron 2013;77:43–57. 

 

Methods that will be used

Standard molecular biology techniques, protein biochemistry, immunohistochemistry, quantitative confocal microscopy, in vivo 2 Photon microscopy, Calcium imaging, neuronal and glial primary cell culture, in vivo mouse work, rodent behavioral pain assessments.

Collaboration Partners:

Members of Heidelberg Pain Consortium SFB1158. In particular, the PhD candidate will strongly collaborate with the group of Dr. Amit Agarwal (UniHD) and Prof. Frank Kirchhoff (Uni Saarland) in the frame of the SFB 1158 project A09N. The recruited student will be part of the group of Prof. Rohini Kuner working directly with Dr. Manuela Simonetti.
 

Profile of candidate’s qualification

We are looking for a highly motivated and enthusiastic PhD candidate. Applicants should hold a diploma/Masters in a biomedical, Life science (i.e. M.S. in Biology, Biochemistry, Neurobiology, Neuscience, Medicine) or related disciplines. Strong analytical and technical skills as well as ability to work in a team and independently plan and conduct experimental research are essential. Furthermore, the candidate should demonstrate a problem-solving, proactive attitude. A background and hands-on laboratory experience in molecular cell biology and biochemistry as well as animal handling experience will be strongly preferred. Since we provide an international working environment, good English language skills are required (no German language requirement) 
 

Keywords:

mouse pain behavior, neuron-glia comunication, cell signaling, calcium imaging, in vivo 2P microscopy 

Multiscale correlational imaging of structural brain changes during chronic pain


Project leader: Thomas Kuner / Johannes Knabbe / Livia Asan

Email:

Application Deadline:

30 September 2019

Start of the project:

at the earliest

Project Description: 

We are looking for a highly motivated doctoral candidate (Dr. rer. nat. or Dr. sc. hum.) in an ongoing study on chronic pain. Experience in fluorescence microscopy, data analysis tools (programming, matlab, scripting) and animal experimentation (Felasa-B) is advantageous, but not a prerequisite to successfully compete for the position.

Project description:

Background: Magnetic resonance imaging (MRI) studies have shown that chronic pain is accompanied by altered brain grey matter volume (GMV) in humans and rodent models. The physical and cellular underpinnings of these structural changes and their causal relationship to chronic pain remain elusive.

The aim of the thesis will be to define cellular correlates for the GMV changes in chronic pain in a correlative imaging study with mice.

The candidate will profit from the rich methodological expertise in our lab and learn and perform

  • Two-photon in vivo imaging
  • Rodent models for neuropathic pain (Spared Nerve Injury) and other pain types
  • Behavioral testing
  • Small animal MRI (in cooperation with ZI Mannheim, AG Weber-Fahr)
  • Participation in the development of a machine learning-based workflow for automatic analysis of the image data in cooperation with our informatics department

The project is embedded in a large successful research consortium on campus for the study of chronic pain, which has been granted extension from the DFG this year (SFB 1158, see https://www.sfb1158.de/index.php). Funding for the PhD position (E13/65%) is granted by the SFB. Young scientists are especially promoted and encouraged through an extensive early career support program. 

References:

    • (1) Grey matter volume changes and corresponding cellular metrics identified in a longitudinal in vivo imaging approach. Livia Asan, Claudia Falfan-Melgoza, Wolfgang Weber-Fahr, Carlo Beretta, Thomas Kuner, Johannes Knabbe. bioRxiv 559765; doi: https://doi.org/10.1101/559765

 

Functional roles and mechanisms of post-translational modifications (PTM) in diabetic peripheral neuropathy (DPN)


Job ID: Kuner_Agarwal0119

 Project leader: Prof. Dr. R. Kuner, Dr. Nitin Agarwal

Application Deadline:

August 15th 2019

Start of PhD project:

October 1st 2019

Source of Funding:

SFB 1118

Project Description:

PTM constitute a key mode of regulation of protein function and localization in biological processes. Diabetes is manifest with an increase in the levels of ROS, methylglyoxal (MG) and glyoxal (GL). ROS, produced during metabolic stress, hyperglycemia, etc., directly regulates PTM of target proteins. In this project, we aim to investigate the changes in proteomes and alteration in PTM of proteins in Schwann cells and peripheral neurons at different diabetic stages to understand the modulation of axonopathy by Schwann cell dysfunction in progression of DPN. You will identify and characterize the novel metabolic target(s) of PTM and their impact on the metabolic pathways.

Methods that will be used:

Standard molecular biology techniques, protein biochemistry, quantitative fluorescence microscopy, rodent behavioral assay, advance in vitro methods to study neuronal and Schwann cell interactions.

Profile of candidate’s qualification:

It is expected that the candidate should be highly motivated to conduct competitive research at the interface of biochemistry, molecular biology and behavioral studies. Experience in biochemistry, molecular biology and animal handling is preferred. 

Please send the complete application as a single pdf and should include: A cover letter, two references and/or letters of recommendation, CV, academic transcripts, a personal research statement (1-2 pages) covering specific research interests and career goals.

Collaboration Partners:

We have both national and international partners. 

References:

Rojas DR, Kuner R, Agarwal N. Metabolomic signature of type 1 diabetes-induced sensory loss and nerve damage in diabetic neuropathy. J Mol Med (Berl). 2019 Jun;97(6):845-854. 

Agarwal N, Helmstädter J, Rojas DR, Bali KK, Gangadharan V, Kuner R. Evoked hypoalgesia is accompanied by tonic pain and immune cell infiltration in the dorsal root ganglia at late stages of diabetic neuropathy in mice. Mol Pain. 2018 Jan-Dec;14 

Rojas DR, Tegeder I, Kuner R, Agarwal N. Hypoxia-inducible factor 1α protects peripheral sensory neurons from diabetic peripheral neuropathy by suppressing accumulation of reactive oxygen species. J Mol Med (Berl). 2018 Dec;96(12):1395-1405. 

Njoo C, Agarwal N, Lutz B, Kuner R. The Cannabinoid Receptor CB1 Interacts with the WAVE1 Complex and Plays a Role in Actin Dynamics and Structural Plasticity in Neurons. PLoS Biol. 2015 Oct 23;13(10) 

Simonetti M, Agarwal N, Stösser S, Bali KK, Karaulanov E, Kamble R, Pospisilova B, Kurejova M, Birchmeier W, Niehrs C, Heppenstall P, Kuner R. Wnt-Fzd signaling sensitizes peripheral sensory neurons via distinct noncanonical pathways. Neuron. 2014 Jul 2;83(1):104-21. 

Contact:

Dr. Nitin Agarwal, 

Institute of Pharmacology, INF 366, 69120 Heidelberg 

phone: +49 (0)6221 – 54 16608

e-mail:

Keywords:

Biochemistry, Molecular biology, Rodent behavioral studies, Diabetes, cellular communications.

Cellular mechanisms of nociception and nociceptive modulation in lateral and medial thalamocortical circuits of mice.


Job ID:  SFB1158_Groh_Mease

Project leaders: Alexander GrohRebecca Mease

Application Deadline:

August 15, 2019

Start of PhD project:

October 01, 2019

Source of Funding:

SFB 1158

Project Description:

We are currently seeking two highly motivated and adventurous Ph.D. students to study neuronal and circuit mechanisms of nociception (pain) in the thalamocortical system. The project combines optogenetics and large-scale electrophysiology in mice and is supported by the second funding period of the Heidelberg Pain Consortium SFB1158 (www.sfb1158.de).

Methods that will be used:

electrophysiology, optogenetics, in vivo, behavior, mathematical/computational modeling, patch-clamp, silicon probe

Profile of candidate’s qualification:

A Diploma/Masters in a biomedical (e.g. neuroscience, biology, medicine) or quantitative discipline (e.g. physics, informatics, mathematics, biomedical-engineering). Previous experience in data analysis or programming using MATLAB/Python/R etc. is strongly preferred. Experience in methods to obtain and interpret neurophysiological data, and /or behavioral assays is highly desirable. Applicants with strong analytical skills and a flair for handling large datasets are particularly encouraged to apply. The working language in the lab is English.

Please send the complete application as a single pdf and should include: A cover letter, two references and/or letters of recommendation, CV, academic transcripts, a personal research statement (1-2 pages) covering specific research interests and career goals.

 

 

Optogenetic tools to explore the role of GABA in modulating pre-synaptic and axonal signalling in peripheral C-fibre nociceptors


Job ID: Carr0119

Project leader: PD Dr. Richard Carr

Application Deadline:

15. Aug 2019

Start of PhD project:

1. Oct 2019

Source of Funding:

SFB 1158

 Project Description: 

A reduction in inhibitory control within the spinal dorsal horn has been widely implicated as a prominent contributor to the development of chronic pain. Accordingly, restoration of spinal inhibition offers a rational and attractive therapeutic strategy. However, the substrates of spinal inhibitory circuits and the mechanisms underlying their disinhibition remain open questions. This project sets out to identify micro-circuits mediating interactions between non-nociceptive and nociceptive signals in the spinal dorsal horn with a focus on circuits involving GABAergic interneurons that make presynaptic inhibitory contacts onto the central terminals of primary nociceptor afferents. The project will specify which functional classes of primary afferent Aδ and C-fibre nociceptors are amenable to pre-synaptic modulation by virtue of their expression of axonal GABAA receptors.

Methods that will be used: 

Chloride imaging, single fibre electrophysiology, corneal nerve terminal electrophysiology, optogenetic neural modulation, numerical simulations in silico 

 Profile of candidate’s qualification:

Graduates from the life sciences, mathematics, physics, engineering or medicine would be well suited. We are looking for a PhD candidate with an interest in optical tools and their application to biological problems, ideally with a leaning towards understanding biological mechanisms using predicative in silico techniques. Skills with Office, Matlab/Igor/Labview or drawing software would be helpful but not requisite. Training for all techniques will be provided during the candidature including technical courses and FELASA accreditation.

Collaboration Partners: 

Stefan Lechner (Heidelberg, Germany) 
Valerio Magnaghi (Milan, Italy) 
Nicolas Petersen (Copenhagen, Denmark)

References:

Klein et al (2017) JNeurosci, 37, 5204-5214 
Sittl et al (2012) PNAS, 109, 6704-9 
Carr et al (2010) PlosONE, 5, e8780

 

Functional and structural plasticity following spinal cord injury: contributions to chronic central neuropathic pain


Job ID:  SFB1158_Puttagunta

Project leaders: Radhika Puttagunta

Application Deadline:

August 15, 2019

Start of PhD project:

October 01, 2019

Source of Funding:

SFB 1158

Project Description:

The overarching goal of this project is to understand the underlying mechanisms that transpire after spinal cord injury that lead toward half of all spinal cord injury (SCI) patients suffering from neuropathic pain. We examine the structural changes observed after SCI and how they relate to pain profiles as well as what initiates these alterations. This continuation work is cited in our publications as well as listed methods below that will be utilized to provide novel targets of therapeutic potential.

Methods that will be used:

Intersectional genetics, cell-specific ablations, use of reporter lines, monosynaptic tracing, tissue clearing and 3D microscope reconstruction, behavioural pain assessments and histology.‚Äč 

Profile of candidate’s qualification:

We search for a M.Sc. student in molecular and cellular neuroscience, biochemistry, genetics or pain research to fill a TV-L salary scale, pay grade E13, up to 4 years to forge collaborative work within the Pain SfB1158 community and abroad along with interest in translational neuroscience.  We provide an international working environment with English as the working language but recommend a background in German.  Given the project it is important the student will obtain certification to work with animals (FELASA Cat. B) and have some experience in microscopy. 

Publications:

  1. Sliwinski C, Nees TA, Puttagunta R, Weidner N, Blesch A. J Neurotrauma Sept 15; 35(18):2222-2238, 2018
  2. Nees TA, Tappe-Theodor A, Sliwinski C, Motsch M, Rupp R, Kuner R, Weidner N, Blesch A. Pain 157 (3):687-697, 2016
  3. Nees TA, Finnerup NB, Blesch A, Weidner N. Pain Mar; 158(3):371-376, 2017. Review.

 

Role of the neurovascular unit in pain-induced spinal sensitization


 Job ID: Ruiz_de_Almodovar0119

Project leader: 

Prof. Dr. Carmen Ruiz de Almodovar

 

Application Deadline:

15 August 2019

Start of PhD project:

01 October 2019

Project Description:

This project is focused on understanding the alterations that may occur in the neurovascular (NVU) unit during conditions of chronic pain. We aim to elucidate whether cellular interactions, or the molecular signalling, within the NVU are altered in the context of chronic pain. Based on Prof. Mauceri’s previous findings, this project also aims to elucidate whether alterations in the neurovascular unit result in the observed pain-associated epigenetic changes in spinal cord neurons.

The recruited student for Ruiz de Almodóvar’s group will focus on understanding the changes in the NVU using different transgenic mouse lines and approaches. The epigenetic part of the project will be performed by Prof. Mauceri’s team. The recruited student will be part of the group of Carmen Ruiz de Almodóvar, who will be the supervisor of the PhD student.

Methods that will be used:

mouse genetics; in vivo mouse work; histology; high resolution microscopy; molecular biology; biochemistry.

 Profile of candidate’s qualification:

Highly motivated student willing to work in a dynamic international environment. 

Background in neuroscience, cellular biology and/or biochemistry.References:

Karakatsani A , Shah B, Ruiz de Almodovar C. Blood vessels as regulators of neural stem cell properties. Front Mol Neurosci. 2019. Apr 12

Paredes I, Himmels P, Ruiz de Almodóvar C. Neurovascular Communication during CNS Development. Dev Cell. 2018 Apr 9;45(1):10-32. 

Himmels P, Paredes I, Adler H, Karakatsani A, Luck R, Marti HH, Ermakova O, Rempel E, Stoeckli ET & Ruiz de Almodovar C. Motor neurons control blood vessel patterning in the developing spinal cord. Nat Commun. 2017 Mar 6;8:14583. 

 

 

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